Estimation of the hemoglobin glycation rate constant.

In a previous study, a method of obtaining mean erythrocyte age ([Formula: see text]) from HbA1c and average plasma glucose (AG) was proposed. However, the true value of the hemoglobin glycation constant ([Formula: see text] dL/mg/day), required for this model has yet to be well characterized. Another study also proposed a method of deriving [Formula: see text] from erythrocyte creatine (EC). Utilizing these formulae, this study aimed to determine a more accurate estimate of [Formula: see text]. One hundred and seven subjects including 31 patients with hemolytic anemia and 76 subjects without anemia were included in this study. EC and HbA1c data were analyzed, and [Formula: see text] using HbA1c, AG and the newly-derived constant, [Formula: see text] were compared to [Formula: see text] using traditional [Formula: see text] in three patients whose data were taken from previous case studies. A value of [Formula: see text] dL/mg/day was determined for [Formula: see text]. [Formula: see text] using HbA1c, AG and [Formula: see text] were found to no be significantly different (paired t-test, [Formula: see text]) to [Formula: see text] using traditional [Formula: see text]. [Formula: see text] enables the estimation of [Formula: see text] from HbA1c and AG.

Long term outcomes from lymphatic venous anastomosis after total hysterectomy to prevent postoperative lymphedema in lower limb.

BACKGROUND: Lymphedema in lower limb is one of major postoperative complications followed by a total hysterectomy with lymph node dissection. The objective of this report is to examine a long-term result of lymphaticovenous anastomosis procedure as a preventive surgery. METHODS: Sixteen patients with endometrial cancer underwent an abdominal hysterectomy with a bilateral salpingo-oophorectomy. Just after pelvic lymph node dissection, either end-to-end or sleeve anastomosis utilizing venules and suprainguinal lymph vessels was performed. During the observation period from 4 to 13 years, the symptom of lymphedema in lower extremities has been assessed. RESULTS: Among 16 patients, 1 presented postoperative lymphedema grade 3 (CTCAE (Common Terminology Criteria for Adverse Events) Ver. 4.0, 10025233) in lower limb, and a second surgery at 7 years after the first one was required. Other 6 patients showed non-severe symptoms of lymphedema, diagnosed as grade 1. The rest 9 patients did not show any symptoms of postoperative lymphedema in a long term (up to 13 years). CONCLUSION: From the long term outcomes of our 16 cases, we propose that a direct lymphaticovenous microsurgery immediately after a hysterectomy with lymphadenectomy of external inguinal lymph node is one of the appropriate therapeutic choices to prevent severe lymphedema in lower limb.

HbA1c adjusted by erythrocyte creatine is a useful glycemic control indicator in patients with hemolysis.

OBJECTIVES: HbA1c shows low in patients with hemolysis, whereas glycated albumin (GA) is not affected by hemolysis. Therefore, the GA/HbA1c ratio reflects hemolysis in diabetic patients with hemolysis. Erythrocyte creatine (EC) is an indicator of hemolysis that reflects the mean erythrocyte age. The aim of this study was to examine whether HbA1c adjusted by EC accurately reflected glycemic control in patients with hemolysis. MATERIALS AND METHODS: A total of 238 individuals, consisting of 131 diabetic patients and 107 non-diabetic subjects, and consisting of 42 patients with hemolysis, and 196 subjects without hemolysis were selected for the study. HbA1c expressed in the IFCC units (iA1c) as well as in the NGSP units (A1C) were used. From the fact that EC and the GA/iA1c ratio showed a significant positive correlation, a formula for iA1c adjusted by EC (ECadj-iA1c) was created from a regression equation between EC and the GA/iA1c ratio. RESULTS: Significant correlations were observed between the GA/iA1c ratio and various hemolytic indicators but not between the GA/ECadj-iA1c ratio and those hemolytic indicators. The GA/iA1c ratio in individuals with hemolysis was significantly higher than in individuals without hemolysis, while no significant differences were observed in the GA/ECadj-iA1c ratio between the groups. Further, iA1c concentrations in non-diabetic patients with hemolysis were significantly lower than in the non-diabetic subjects without hemolysis, whereas ECadj-iA1c and GA concentrations showed no significant difference between the two groups. CONCLUSIONS: These results suggested that ECadj-iA1c accurately reflected glycemic control in patients with hemolysis.

Nuclear co-expression of p21 and p27 induced effective cell-cycle arrest in T24 cells treated with BCG.

A proposed mechanism underlying the effect of bacillus Calmette-Guérin (BCG) treatment for bladder cancer cells is as follows: BCG-induced crosslinking of cell-surface receptors results in the activation of signaling cascades, including cell-cycle regulators. However, the clinical significance of cell-cycle regulators such as p21 and p27 is controversial. Here we investigated the relationship between BCG exposure and p21 and p27. We used confocal laser microscopy to examine the expression levels of pKi67, p21 and p27 in T24 cells (derived from human urothelial carcinoma) exposed six times to BCG. We performed dual immunofluorescence staining methods for p21 and p27 and observed the localization of nuclear and cytoplasm expressions. We investigated the priority of p27 over p21 regarding nuclear expression by using p27 Stealth RNAi™ (p27-siRNA). With 2-h BCG exposure, the nuclear-expression level of p21 and p27 was highest, while pKi67 was lowest. The percentage of double nuclear-expression of p21 and p27 in BCG cells was significantly higher than that in control cells during the 1st to 6th exposure (P < 0.05), and the expression of pKi67 showed the opposite of this pattern. Approximately 10% of the nuclear p21 was independent of p27, whereas the cytoplasmic p21 was dependent on p27. Our results suggested that the nuclear co-expression of p21 and p27 caused effective cell-cycle arrest, and thus the evaluation of the nuclear co-expression of p21 and p27 might help determine the effectiveness of BCG treatment.

Shortened mean erythrocyte age in female patients with type 2 diabetes mellitus.

BACKGROUND: The hyperglycemic state is known to shorten the erythrocyte life span. Erythrocyte creatine (EC) reflects the mean erythrocyte age and is useful as an indicator of hemolysis. Here, we studied the relationship between EC and glycemic control indicators [HbA1c or glycated albumin (GA)] in non-diabetic subjects and diabetic patients. METHODS: This study included 119 patients with type 2 diabetes mellitus (T2DM) and 76 non-diabetic subjects matched by sex and age. We studied the relationships between EC and HbA1c or GA in patients with T2DM and non-diabetic subjects. RESULTS: Erythrocyte creatine in T2DM patients was significantly higher than that in non-diabetic subjects, and the ratio of high EC levels (>1.8 µmol/g Hb) in T2DM patients was significantly higher as well. Furthermore, female EC was significantly higher than male EC, and the ratio of high EC levels in females was significantly higher than in the males as well. While male EC had no significant correlation with HbA1c or GA, female EC had significant positive correlations with both. Male EC had no significant difference between T2DM patients and non-diabetic subjects, while the EC in female patients with T2DM was significantly higher than in female non-diabetic subjects. CONCLUSIONS: The significant positive correlations of EC with HbA1c and GA in female patients with T2DM suggested that the mean erythrocyte age decreased in female diabetic patients with poor glycemic control.

Preoperative Chemoradiotherapy in Locally Advanced Bulky Squamous Cell Carcinoma of the Uterine Cervix.

OBJECTIVES: The aim of this study was to evaluate long-term survival and feasibility in patients with bulky squamous cell carcinoma of the uterine cervix who underwent surgery after concurrent chemoradiotherapy. METHODS: A review of patients with locally advanced bulky squamous cell cervical cancer who underwent chemoradiation followed by surgery with pelvic lymphadenectomy was performed. Chemoradiotherapy included 2 monthly doses of intra-arterial chemotherapy with cisplatin (50 mg/m) and mitomycin C (10 mg/body) and external irradiation to the whole pelvis and high-dose-rate brachytherapy. From 2000 to 2006, 23 patients were enrolled in a single institution. Patient distribution according to the International Federation of Gynecology and Obstetrics stage was as follows: 9 stage IB2, 10 stage IIB, and 4 stage IIIB. Radiological lymph node involvement was present in 69.6% (16/23), including 2 cases of para-aortic lymph node swelling. The radiological response, pathological response, overall and disease-free survival, and late complications were assessed. RESULTS: Among the patients, 12 (52.2%) showed pathological complete response, and 11 (47.8%) showed a pathological partial response for cervical lesions. Among the cases of radiological pelvic lymph node swelling, the response rate was 93.3% (14/15). Only 1 case showed viable cancer cells in the resected pelvic lymph nodes among radiological complete response cases. In the median follow-up duration (121 months; range, 17-180 months), the 5-year overall survival and disease-free survival were 95.7% and 86.7%, respectively. Seven events in 4 patients led to the development of postoperative fistula formation requiring a rescue surgery. CONCLUSIONS: Chemoradiotherapy followed by surgery was effective for patients with bulky squamous cell carcinoma of the uterine cervix. Further investigation to select suitable patients for this multimodal treatment will be required.

Binucleated HeLa cells are formed by cytokinesis failure in starvation and keep the potential of proliferation.

Many cytological studies have reported that the numbers of binucleated cells were elevated in various tumors. However, binucleated cells are observed in not only malignant tumors but also normal tissues. Thus, the clinical significance of binucleated cells is controversial. Here we attempted to elucidate the characteristics of binucleated HeLa cells using time-lapse microscopy. To examine the frequency, viability, proliferation, and formation mechanism of binucleated cells, we grew HeLa cells on chamber slides and tissue culture dishes in DMEM supplemented with (10, 3, 1 and 0.5 % media) and without fetal bovine serum (0 % medium). The proliferation was evaluated by the medium improvement examination (cultured for 2 more days in 10% medium after culturing in 0% medium; starvation). In the 0 % medium, 150 binucleated cells were formed by cytokinesis failure. There were significantly more binucleated cells in the 0 % medium than in the 10, 3, 1 and 0.5 % media. About twice the number of binucleated cells underwent mitosis in the improvement examinations than in the serum-free examination. We found here that starvation induced the binucleation of HeLa cells and that some binucleated cells can reproduce. These findings might be helpful for understanding binucleated cells in tumors.

A lower serum level of middle-molecular-weight adiponectin is a risk factor for endometrial cancer.

BACKGROUND: The present study was undertaken to examine the correlation between serum levels of adiponectin isoforms and the risk for endometrial cancer. METHODS: This retrospective case-control study included 43 Japanese women with endometrial cancer and 62 Japanese women with no history of cancer. Serum levels of total adiponectin and the respective isoforms were determined by enzyme-linked immunosorbent assay. Multivariate logistic regression analysis was performed on the serum levels of total adiponectin and its isoforms, high molecular weight, middle molecular weight, and low molecular weight adiponectins, after adjustment for confounders (age, body mass index, hypertension, and diabetes mellitus). RESULTS: The distribution of body mass index revealed a statistically significant difference between patients and controls (P = 0.001). A statistically significant difference (P < 0.01) was also found in the incidence of diabetes mellitus between the two groups, although there was no significant difference in the incidence of hypertension. In controls, an inverse correlation was observed between body mass index and serum adiponectin levels. However, in patients, an inverse correlation was found only between body mass index and serum middle molecular weight adiponectin level. After adjustment for confounding variables, the factor found to be most closely associated with endometrial cancer was a lower serum level of middle molecular weight adiponectin (adjusted odds ratio 4.89, 95 % confidence interval value 1.25-19.11, P = 0.022). CONCLUSION: Low serum level of middle molecular weight adiponectin was the only independent risk factor for endometrial cancer suggesting that the application of adiponectin might prevent or decrease the risk for endometrial cancer.

Pyomyositis associated with chemotherapy for endometrial cancer: a case report.

Pyomyositis is a rare complication of chemotherapy for non-hematological malignancies. A 58-year-old woman with endometrial carcinoma, in whom pyomyositis developed during adjuvant chemotherapy, was presented in this report. After initiating empiric antibiotic therapy for febrile neutrocytopenia, screening CT showed multiple abscesses in the lower limbs. Operative drainage of the abscess was effective.

Association between carotenoids and outcome of cervical intraepithelial neoplasia: a prospective cohort study.

BACKGROUND: It has been suggested that micronutrients such as alpha-tocopherol, retinol, lutein, cryptoxanthin, lycopene, and alpha- and beta-carotene may help in the prevention of cervical cancer. Our aim was to investigate whether serum concentrations and/or dietary intake of micronutrients influence the regression or progression of low-grade cervical abnormalities. METHODS: In a prospective cohort study of 391 patients with cervical intraepithelial neoplasia (CIN) grade 1-2 lesions, we measured serum micronutrient concentrations in addition to a self-administered questionnaire about dietary intake. We evaluated the hazard ratio (HR) adjusted for CIN grade, human papillomavirus genotype, total energy intake and smoking status. RESULTS: In non-smoking regression subjects, regression was significantly associated with serum levels of zeaxanthin/lutein (HR 1.25, 0.78-2.01, p = 0.024). This benefit was abolished in current smokers. Regression was inhibited by high serum levels of alpha-tocopherol in smokers (p = 0.042). In progression subjects, a significant protective effect against progression to CIN3 was observed in individuals with a medium level of serum beta-carotene [HR 0.28, 95 % confidence interval (CI) 0.11-0.71, p = 0.007), although any protective effect from a higher level of serum beta-carotene was weaker or abolished (HR 0.52, 95 % CI 0.24-1.13, p = 0.098). Increasing beta-carotene intake did not show a protective effect (HR 2.30, 95 % CI 0.97-5.42, p = 0.058). CONCLUSIONS: Measurements of serum levels of carotenoids suggest that regression is modulated by smoking status. Maintaining a medium serum level of beta-carotene has a protective effect for progression; however, carotene intake is not correlated with serum levels of carotenoids.

Do neutralizing antibody responses generated by human papillomavirus infections favor a better outcome of low-grade cervical lesions?

To determine the role of neutralizing antibody generated by human papillomavirus (HPV) infections, baseline levels of serum neutralizing antibodies directed against HPV 16 and cervical HPV DNA were determined in 242 unvaccinated women with low-grade cervical abnormalities, who were then monitored by cytology and colposcopy every 4 months. In women infected with HPV 16 (n = 42), abnormal cytology persisted longer in those positive for HPV 16-specific neutralizing antibodies at baseline (median time to cytological regression: 23.8 vs. 7.2 months). Progression to cervical precancer (cervical intraepithelial neoplasia grade 3) within 5 years occurred only among women carrying HPV 16-specific neutralizing antibodies (P = 0.03, log-rank test). In women infected with types other than HPV 16 (n = 200), detection of HPV 16-specific neutralizing antibodies was not correlated with disease outcome. In conclusion, development of specific neutralizing antibodies following natural HPV 16 infection did not favor a better outcome of low-grade cervical lesions induced by HPV 16 or by other types; rather, detection of neutralizing antibodies generated by current infection may reflect viral persistence and thus help identify those who are at high risk of disease progression.

HLA class II DRB1*1302 allele protects against progression to cervical intraepithelial neoplasia grade 3: a multicenter prospective cohort study.

OBJECTIVE: Genetic variations in human leukocyte antigens (HLA) class II regions may influence the risk of cervical cancer by altering the efficiency of the immune responses to human papillomavirus antigens. This prospective study was designed to evaluate the effects of HLA class II alleles on the natural course of cervical precursor lesions. METHODS: We followed a total of 454 Japanese women with cytological low-grade squamous intraepithelial lesion (LSIL) and histological cervical intraepithelial neoplasia grades 1 to 2 (CIN1-CIN2). Patients were tested for HLA class II alleles and cervical human papillomavirus DNA at the time of entry and then monitored by cytology and colposcopy every 4 months for a mean follow-up of 39.0 months. We analyzed cumulative probabilities of cytological regression to at least 2 consecutive negative Papanicolaou tests and histological progression to biopsy-positive CIN3. RESULTS: During the follow-up period, 39 lesions progressed to CIN3, and 282 lesions regressed to normal cytology. Progression to CIN3 did not occur in DRB1*1302-positive women, and this protective effect of DRB1*1302 was statistically significant (P = 0.03). Low-grade squamous intraepithelial lesion regressed to normal cytology more quickly in DRB1*1302-positive women than in DRB1*1302-negative women (median time, 8.9 months vs 14.2 months), although the difference was not statistically significant (P = 0.16). The risk of LSIL persistence or progression to CIN3 within 5 years was not affected by any other HLA class II alleles. CONCLUSION: By using a prospective study design, we demonstrated the protective effect of the DRB1*1302 allele against progression to CIN3 among Japanese women with LSIL.

The usefulness of combined measurements of squamous cell carcinoma antigens 1 and 2 in diagnosing atopic dermatitis.

BACKGROUND: The squamous cell carcinoma antigen (SCCA) is widely used as a serological biomarker for various cancers. There are two known SCCA molecules, SCCA1 and SCCA2. We previously found that interleukin-4 or interleukin-13, two related Th2-type cytokines that play an important role in allergic diseases, induce expression of SCCA1 and SCCA2. In this study, we examined whether combined measurements of SCCA1 and SCCA2 are useful for diagnosing atopic dermatitis (AD). METHODS: We established new enzyme-linked immunosorbent assays (ELISAs) to specifically detect SCCA1 or SCCA2. We applied serum samples from AD patients with food allergies and from cervical cancer patients to these ELISAs. We performed receiver operating characteristic analyses to diagnose AD and to distinguish AD from cervical cancer. RESULTS: Serum concentrations of both SCCA1 and SCCA2 were elevated in AD patients. The serum concentrations of SCCA1 and SCCA2 positively correlated with the clinical severity of AD, showing high specificity (0.86-0.88) and sensitivity (0.86) against control donors. The serum concentrations of SCCA1 and SCCA2 were elevated in cervical cancer patients; however, the SCCA2/SCCA1 ratios clearly distinguished AD patients from cervical cancer patients with high specificity (0.87) and sensitivity (0.87). Expression of SCCA2 was predominant in AD patients, whereas cervical cancer patients showed a predominance of SCCA1. CONCLUSIONS: Combined measurements of SCCA1 and SCCA2 are very useful in estimating the severity of allergic diseases, making it possible to distinguish allergic diseases from cancers.

Subsequent risks for cervical precancer and cancer in women with low-grade squamous intraepithelial lesions unconfirmed by colposcopy-directed biopsy: results from a multicenter, prospective, cohort study.

OBJECTIVE: To investigate the natural course of low-grade squamous intraepithelial lesions (LSILs) that cannot be histologically confirmed by colposcopy-directed biopsy. METHODS: In a multicenter, prospective, cohort study of Japanese women with LSILs, we analyzed the follow-up data from 64 women who had a negative biopsy result at the initial colposcopy (biopsy-negative LSIL) in comparison with those from 479 women who had a histologic diagnosis of cervical intraepithelial neoplasia grade 1 (LSIL/CIN1). Patients were monitored by cytology and colposcopy every 4 months for a mean follow-up period of 39.0 months, with cytologic regression defined as two consecutive negative smears and normal colposcopy. RESULTS: In women with biopsy-negative LSILs, there were no cases of CIN3 or worse (CIN3+) diagnosed within 2 years; the difference in the 2-year risk of CIN3+ between the two groups was marginally significant (0 vs. 5.5%; P = 0.07). The cumulative probability of cytologic regression within 12 months was much higher in the biopsy-negative LSIL group (71.2 vs. 48.6%; P = 0.0001). The percentage of women positive for high-risk human papillomaviruses (hrHPVs) was significantly lower in the biopsy-negative LSIL group than in the LSIL/CIN1 group (62.1 vs. 78.4%; P = 0.01); however, the 12-month regression rate of biopsy-negative LSIL was similar between hrHPV-positive and -negative women (67.3 vs. 74.4%, P = 0.73). CONCLUSION: In women with biopsy-negative LSILs, the risk of CIN3+ diagnosed within 2 years was low; furthermore, approximately 70% underwent cytologic regression within 12 months, regardless of HPV testing results. Biopsy-negative LSILs may represent regressing lesions rather than lesions missed by colposcopy.

Predicting the progression of cervical precursor lesions by human papillomavirus genotyping: a prospective cohort study.

Only a subset of cervical precursor lesions progress to cervical cancer and because of the lack of the predictive markers, it cannot be ascertained which lesions will progress or not. To estimate the risk of disease progression associated with human papillomavirus (HPV) genotypes, we followed 570 Japanese women with cytological LSIL (low-grade squamous intraepithelial lesion) and histological CIN (cervical intraepithelial neoplasia) grade 1-2 lesions (479 CIN 1; 91 CIN 2) at 3 to 4 month intervals for a mean follow-up period of 39.1 months. At entry, we detected HPV DNA in cervical samples by polymerase chain reaction-based methodology. Over the period of follow-up period, 46 lesions progressed to CIN 3 while 362 regressed to normal cytology. Women with multiple HPV infections were more likely to have persistent lesions (hazard ratio [HR] for regression, 0.65; 95% confidence interval [CI], 0.42-1.02; p = 0.07); however, multiple infections did not increase the risk of progression (HR for progression, 1.04; 95% CI, 0.37-2.94; p = 0.94). After adjusting for CIN grade and women's age, HRs for progression to CIN 3 (vs. women with low-risk types or negative for HPV DNA) varied markedly by HPV genotype: type 16 (11.1, 95% CI: 1.39-88.3); 18 (14.1, 0.65-306); 31 (24.7, 2.51-243); 33 (20.3, 1.78-231); 35 (13.7, 0.75-251); 52 (11.6, 1.45-93.3); 58 (8.85, 1.01-77.6); other high-risk types (4.04, 0.47-34.7). HPV 45 was not detected in our study subjects. The cumulative probability of CIN 3 within 5 years was 20.5% for HPV 16, 18, 31, 33, 35, 52 and 58; 6.0% for other high-risk types; 1.7% for low-risk types (p = 0.0001). In conclusion, type-specific HPV testing for women with LSIL/CIN 1-2 lesions is useful for identifying populations at increased or decreased risk of disease progression.

Tuberous sclerosis complex associated with papillary serous carcinoma of the peritoneum, lymphangioleiomyomatosis, and angiomyolipoma.

Tuberous sclerosis complex (TSC) is associated with benign and malignant tumors, including lymphangioleiomyomatosis (LAM) and angiomyolipoma (AML). We herein describe the TSC case of a 50-year-old woman having a papillary serous carcinoma of the peritoneum (PSCP), LAM, and AML. On microscopic examination, the PSCP cells showed a cuboidal to columnar shape, proliferated into the papillae, and infiltrated into the peritoneal cavity and anterior thoracic wall. On immunohistochemical evaluation, the tumor cells were positive for epithelial membrane antigen, human epidermal cytokeratins, and progesterone receptor, but negative for calretinin, carcinoembryonic antigen, MCF-7 cell line (Ber-EP4), and estrogen receptor.

Evidence-based guidelines for treatment of uterine body neoplasm in Japan: Japan Society of Gynecologic Oncology (JSGO) 2009 edition.

Endometrial carcinoma is one of the most common gynecologic malignancies in Japan and its incidence has increased recently. Although surgery is the cornerstone of the management of patients with endometrial cancer, there is significant variation in Japan with regard to the type of hysterectomy employed. Additionally, it remains controversial whether full nodal staging is required in all patients. Furthermore, adjuvant therapy differs between Japan and Western countries. To delineate clearly the standard of care for endometrial cancer treatment in Japan, the guidelines for the treatment of endometrial cancer were published in 2006 and revised in 2009. The 2009 edition included topics not addressed in the previous edition including the treatment of mesenchymal tumors, for example leiomyosarcoma, and sections covering the treatment of serous and clear-cell adenocarcinoma. These guidelines are composed of nine chapters and include nine algorithms. The guidelines also contain fifty-one clinical questions (CQs) and each CQ consists of recommendations, background, explanations, and references. The treatment recommendations herein are tailored to reflect current Japanese clinical practice and ensure equitable care for all Japanese women diagnosed with endometrial cancer.

Tobacco smoking and regression of low-grade cervical abnormalities.

The role of tobacco smoking in the multistage carcinogenesis at the cervix is not fully understood because of a paucity of prospective data. To assess the relationship between smoking and spontaneous regression of cervical precursor lesions, a total of 516 women with low-grade squamous intraepithelial lesion (LSIL) were monitored by cytology and colposcopy every 4 months. Probability of LSIL regression within 2 years was analyzed in relation to smoking behaviors, with regression defined as at least two consecutive negative Pap smears and normal colposcopy. Women's age, initial biopsy results, and human papillomavirus (HPV) genotypes were included in the multivariate models for adjustments. Our study subjects included 258 never-smokers and 258 smokers (179 current and 79 former smokers). During a mean follow-up time of 39.8 months, 320 lesions regressed to normal cytology. Probability of regression within 2 years was significantly lower in smokers than in never-smokers (55.0%vs 68.8%, P = 0.004). The risk of LSIL persistence increased with smoking intensity and duration and with younger age at starting smoking (P = 0.003, P < 0.001, and P = 0.03, respectively). Smokers had twice as high a risk of persistent HPV infection compared to never-smokers (odds ratio, 2.50; 95% confidence interval, 1.30-4.81; P = 0.006). In young women, passive smoking since childhood reduced probability of regression within 2 years (56.7%vs 85.9%, P < 0.001). Further adjustments for a wide range of cervical cancer risk factors did not change the findings. In conclusion, tobacco smoking may interfere with regression of cervical precursor lesions. Childhood exposure to second-hand smoke may increase a risk of persistent cervical abnormalities among young women.